There is a major need for biomaterials that provide improved regeneration of craniofacial tissue and dental defects, where control of interfaces and osteogenesis can be tailored. Specifically, bone regeneration and titanium-bone interfaces are two key areas where improvements in interfacial bonding and bone remodeling are in need of advancements. In this renewal proposal, we build upon our progress in the current grant where we established the foundation for a new family of highly tailored biomaterials for bone regeneration based on silk-silica nanocomposites. Specifically, control of the organic (silk) and inorganic (silica) domains, based on bioengineering and chemistry approaches, and subsequent success in bone regeneration, lays the groundwork for this renewal. Our hypothesis is that this bioengineering approach to biomaterial design, and in particular organic-inorganic nanocomposite systems, can be exploited towards the design of multifunctional biomaterial systems for bone tissue regeneration. Tight control of chemistry, sequence, assembly and material functions (osteogenesis) can be tailored using this approach. We plan to expand the functional features of this new family of chimeric proteins by adding selective bone binding and titanium binding peptides to optimize interfaces, and also include antimicrobial components. These new systems will be evaluated in vitro related to osteogenic markers from hMSCs and mechanisms, and then in vivo in animal models to explore bone interfaces, bone formation and titanium anchoring in bone, as critical needs in the craniofacial and dental fields. The ability to tailor the chemistry and structure of such highly controlled multifunctional biomaterials to regulate the size and morphology of the silica phase, allows the formation of nano-scale composites required in craniofacial and dental repair scenarios. We plan to expand these systems with new functions to provide a novel path forward for improved interfaces in concert with the silica components, such that a new family of biomaterial scaffold designs will be achieved to match craniofacial and dental repair needs. The unprecedented control of all features of these novel chimeric protein biomaterials, due to the design features embedded in the bioengineering approach, has implications for a wide range of new biomaterials for tissue interfaces and tissue regeneration.